Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMRWSKX)

• Drug Name: Afegostat Drug Info
• Synonyms: Isofagomine; (3R,4R,5R)-5-(HYDROXYMETHYL)PIPERIDINE-3,4-DIOL; 169105-89-9; iso-Fagomine; D-Isofagomine; UNII-G23AP190YS; 5-HYDROXYMETHYL-3,4-DIHYDROXYPIPERIDINE; CHEMBL206468; G23AP190YS; IFM; 5-Hydroxymethyl-3,4-piperidinediol; (3R,4R,5R)-5-(HYDROXYMETHYL)PIPERIDINE-3,4-DIOL HYDROCHLORIDE; Afegostat [USAN:INN]; 1oif; Afegostat (USAN/INN); SCHEMBL581577; GTPL7410; 3,4-piperidinediol, 5-(hydroxymethyl)-, (3R,4R,5R)-; DTXSID20168651; 5-Hydroxymethylpiperidine-3,4-diol; ZINC3813668; BDBM50182801; AKOS006348872; DB04545; HY-14829; CS-0003581; D09576; Q21396373; (3R,4R,5R)-5-(Hydroxymethyl)piperidine-3,4-diol, 8; Afegostat; isofagomine; (3R,4R,5R)-5-(HYDROXYMETHYL)PIPERIDINE-3,4-DIOL

Indication

Disease Entry	ICD 11	Status	REF
Gaucher disease	5C56.0Y	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 447607
  CAS Number: CAS 169105-89-9
  TTD Drug ID: DMRWSKX

Molecule-Related Drug Atlas

Drug(s) Targeting Glucosylceramidase (GBA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Velaglucerase alfa	DM4BOAS	Gaucher disease type I		Approved	[3]
Taliglucerase alfa	DM3PZXN	Metabolic disorder	5C50-5D2Z	Approved	[4]
Isofagomine tartrate	DM2RS0V	Metabolic disorder	5C50-5D2Z	Phase 2	[5]
NCGC607	DMXG0O1	Gaucher disease	5C56.0Y	Preclinical	[6]
N-Octyl-beta-valienamine	DM39C47	Gaucher disease	5C56.0Y	Preclinical	[7]
2-(Acetylamino)-2-Deoxy-a-D-Glucopyranose	DMOUG6Y	Discovery agent	N.A.	Investigative	[8]
L-Isofagomine	DM6RKOC	Discovery agent	N.A.	Investigative	[9]
(2R,3S,4S,5R)-2-propylpiperidine-3,4,5-triol	DM7GI94	Discovery agent	N.A.	Investigative	[10]
N-(Propylamide-acetophenone)-1-deoxynojirimycin	DMXI4V8	Discovery agent	N.A.	Investigative	[11]
(2R,3S,4S,5R)-2-nonylpiperidine-3,4,5-triol	DMIQNX9	Discovery agent	N.A.	Investigative	[10]

Drug(s) Affected By Lysosomal acid glucosylceramidase (GBA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[12]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[12]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[13]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[14]
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[12]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[16]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[17]
Milchsaure	DM462BT	Pruritus	EC90	Investigative	[18]
all-trans-4-oxo-retinoic acid	DMM2R1N	Discovery agent	N.A.	Investigative	[12]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glucosylceramidase (GBA)	TT1B5PU	GLCM_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Lysosomal acid glucosylceramidase (GBA1)	OT0XMD63	GBA1_HUMAN	Gene/Protein Processing	[2]

References

• [1] Lysosomes as a therapeutic target. Nat Rev Drug Discov. 2019 Dec;18(12):923-948.
• [2] Evaluation of quinazoline analogues as glucocerebrosidase inhibitors with chaperone activity. J Med Chem. 2011 Feb 24;54(4):1033-58. doi: 10.1021/jm1008902. Epub 2011 Jan 20.
• [3] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [4] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [5] Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry. Chembiochem. 2008 Nov 3;9(16):2650-62.
• [6] A New Glucocerebrosidase Chaperone Reduces alpha-Synuclein and Glycolipid Levels in iPSC-Derived Dopaminergic Neurons from Patients with Gaucher Disease and Parkinsonism. J Neurosci. 2016 Jul 13;36(28):7441-52.
• [7] Chemical modification of the beta-glucocerebrosidase inhibitor N-octyl-beta-valienamine: synthesis and biological evaluation of 4-epimeric and 4-O-(beta-D-galactopyranosyl) derivatives. Bioorg Med Chem. 2002 Jun;10(6):1967-72.
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [9] In vitro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell cultures. Bioorg Med Chem. 2008 Aug 1;16(15):7330-6.
• [10] Synthesis of new beta-1-C-alkylated imino-L-iditols: A comparative study of their activity as beta-glucocerebrosidase inhibitors. Bioorg Med Chem. 2010 Apr 1;18(7):2645-50.
• [11] Nanomolar affinity, iminosugar-based chemical probes for specific labeling of lysosomal glucocerebrosidase. Bioorg Med Chem. 2010 Jan 1;18(1):267-73.
• [12] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [13] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [16] Benzo(a)pyrene exposure in utero exacerbates Parkinson's Disease (PD)-like -synucleinopathy in A53T human alpha-synuclein transgenic mice. Toxicol Appl Pharmacol. 2021 Sep 15;427:115658. doi: 10.1016/j.taap.2021.115658. Epub 2021 Jul 29.
• [17] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.